Regenerative medicine: transdifferentiation in vivo.

A major challenge in regenerative medicine is the generation of functionally effective target cells to replace or repair damaged tissues. Transdifferentiation in vivo is a novel strategy to achieve cell fate conversion within the native physiological niche; this technology may provide a time- and cost-effective alternative for applications in regenerative medicine and may also minimize the concerns associated with in vitro culture and cell transplantation.

Gating pluripotency via nuclear pores.

In recent years, growing evidence has pointed to the interesting idea that pluripotency might be regulated by a nuclear-pore-coordinated network that controls the level of pluripotency factors in the nucleus. A thorough understanding of this process might improve our comprehension of cell pluripotency and differentiation during embryogenesis, as well as aiding the development of novel models for studying human diseases.

DNA methylome: Unveiling your biological age.

Hannum and colleagues performed DNA methylation sequencing to examine the relationship between DNA methylome and aging rate. Notably, they succeeded in building a quantitative and reproducible model based on the epigenetic bio-markers to predict aging rate with high accuracy. This progress enlightens us in many aspects particularly in applying this novel set of bio-markers on studying the mechanism of aging rate using adult tissue-specific stem cells, building up a potential quantitative model to explore the mechanism for other epigenetic factors like non-coding RNA, and understanding the principle and mechanism of 3D chromatin structure in epigenetic modulation.

Global DNA methylation and transcriptional analyses of human ESC-derived cardiomyocytes.

With defined culture protocol, human embryonic stem cells (hESCs) are able to generate cardiomyocytes in vitro, therefore providing a great model for human heart development, and holding great potential for cardiac disease therapies. In this study, we successfully generated a highly pure population of human cardiomyocytes (hCMs) (>95% cTnT) from hESC line, which enabled us to identify and characterize an hCM-specific signature, at both the gene expression and DNA methylation levels. Gene functional association network and gene-disease network analyses of these hCM-enriched genes provide new insights into the mechanisms of hCM transcriptional regulation, and stand as an informative and rich resource for investigating cardiac gene functions and disease mechanisms.

Concealing cellular defects in pluripotent stem cells.

Inherent and acquired defects in gene expression, protein homeostasis, metabolic pathways, and organelle function are linked to aging and a wide range of human diseases. Although concealed or dormant in the embryonic stage, they often manifest later in life. We review and discuss recent observations on how somatic cells bearing specific phenotypic defects can be reprogrammed into a pluripotent state where most phenotypic abnormalities can be reset or tolerated.

Mitochondrial regulation in pluripotent stem cells.

Due to their fundamental role in energy production, mitochondria have been traditionally known as the powerhouse of the cell. Recent discoveries have suggested crucial roles of mitochondria in the maintenance of pluripotency, differentiation, and reprogramming of induced pluripotent stem cells (iPSCs). While glycolytic energy production is observed at pluripotent states, an increase in mitochondrial oxidative phosphorylation is necessary for cell differentiation.

Progress and prospects in stem cell therapy.

In the past few years, progress being made in stem cell studies has incontestably led to the hope of developing cell replacement based therapy for diseases deficient in effective treatment by conventional ways. The induced pluripotent stem cells (iPSCs) are of great interest of cell therapy research because of their unrestricted self-renewal and differentiation potentials. Proof of principle studies have successfully demonstrated that iPSCs technology would substantially benefit clinical studies in various areas, including neurological disorders, hematologic diseases, cardiac diseases, liver diseases and etc.

"TET-on" pluripotency.

Recent studies have uncovered a specific role of TET proteins in reprogramming somatic cells to induced pluripotent stem cells, a process where O-linked β-N-acetylglucosamine transferase may play a crucial role.

Serum miR-21 and miR-92a as biomarkers in the diagnosis and prognosis of colorectal cancer.

Previous studies from our laboratory identified a number of miRNAs that were aberrantly expressed in colorectal cancer (CRC) tissue. However, their diagnostic and prognostic value in serum has not been fully evaluated. In the present study, we measured the levels of five miRNAs (miR-21, miR-31, miR-92a, miR-18a, and miR-106a) in serum samples from 200 CRC patients, 50 advanced adenoma patients, and 80 healthy controls by real-time quantitative polymerase chain reaction (RT-PCR).

Autophagic control of cell 'stemness'.

Stem cells have the ability to self-renew and differentiate into various cell types. Both cell-intrinsic and extrinsic factors may contribute to aging-related decline in stem cell function and loss of stemness. The maintenance of cellular homeostasis requires timely removal of toxic proteins and damaged organelles that accumulate with age or in pathological conditions.

hESC-derived pancreatic progenitors.

Successful derivation of pancreatic progenitors from human embryonic stem cells (hESCs) in vitro and further differentiation towards functional β cells in vivo may create the possibility of using hESC-derived pancreatic progenitors (PPs), instead of derived β cells, as an alternative transplantable source in β cell replacement therapy. Here we discuss present approaches, as well as future alternatives, in the fields of basic and clinic research on β cell differentiation, derivation and transplantation.

[Mesenchymal stem cells implantation increases the myofibroblasts congregating in infarct region in a rat model of myocardial infarction].

Objective: To investigate the modulation effects of mesenchymal stem cells (MSC) implantation on the myofibroblasts congregating in the infarct region after myocardial infarction (MI).

Methods: MI was induced in SD rats by left anterior descending coronary artery ligation, and the experimental animals were assigned randomly into the sham group, MI + PBS group and MI + MSC group (myocardial injection of 0.1 ml 2×10(7)/ml in four locations in the infarct region).

Reevaluation of the safety of induced pluripotent stem cells: a call from somatic mosaicism.

Recent studies have been raising doubts on the safety of induced pluripotent stem cells (iPSCs) and proposing that the process of reprogramming brought about copy number variations (CNVs) in iPSCs. However, a recent paper published in Nature provided evidence showing that most CNVs were pre-existed as somatic mosaicism but not resulted from the reprogramming. This new finding would profoundly reshape some previous thoughts and endorse the confidence of iPSCs in both research and therapy.

New march towards the regeneration of sensation and cognition: hear more, see more and learn more.

As many human sensory and cognitive diseases are caused by irreversible damage or loss of certain types of neurons, methodologies aimed at replacement of lost neurons are key to restore lost sensation. Recent advances in generation of ear-cell progenitors, optic-cup structures and cortical neurons from human embryonic stem cells and induced pluripotent stem cells provide versatile tools for modeling human diseases and developing cells for replacement therapies.

Beating in a dish: new hopes for cardiomyocyte regeneration.

Functional human cardiomyocytes hold great promise in cell transplantation-based therapy to treat many heart diseases. To meet this devastating and clinical need, researchers are infatuated with developing novel technologies and methodologies to efficiently generate cardiomyocytes through either stem cell differentiation or cell lineage transdifferentiation. Though exciting progress has been made, challenges remain to be addressed before the translation from bench side to bed side can be fulfilled.

Progressive degeneration of human neural stem cells caused by pathogenic LRRK2.

Nuclear-architecture defects have been shown to correlate with the manifestation of a number of human diseases as well as ageing. It is therefore plausible that diseases whose manifestations correlate with ageing might be connected to the appearance of nuclear aberrations over time. We decided to evaluate nuclear organization in the context of ageing-associated disorders by focusing on a leucine-rich repeat kinase 2 (LRRK2) dominant mutation (G2019S; glycine-to-serine substitution at amino acid 2019), which is associated with familial and sporadic Parkinson's disease as well as impairment of adult neurogenesis in mice.

iPSC technology to study human aging and aging-related disorders.

A global aging population, normally accompanied by a high incidence of aging-associated diseases, has prompted a renewed interest in basic research on human aging. Although encouraging progress has been achieved using animal models, the underlying fundamental mechanisms of aging remain largely unknown. Here, we review the human induced pluripotent stem cell (hiPSC)-based models of aging and aging-related diseases.

The dawn of angiogenesis modeling: regenerating vasculature from human pluripotent stem cells.

Efficient generation of functional human vascular endothelial cells and smooth muscle cells from pluripotent stem cells is an extensively studied topic and of great interest in the stem cell field. Though thought to be technically complex and difficult, substantial progress has been made towards this direction. Here we aim to summarize and discuss the most recent advances in this topic and their future perspective in research and clinic.

Huntington's disease: dancing in a dish.

In a recent landmark paper, the Huntington's disease (HD) iPSC Consortium reports on the establishment and characterization of a panel of iPSC lines from HD patients, and more importantly, the successful modeling of HD in vitro. In the same issue of Cell Stem Cell, An et al. reports on the successful targeted gene correction of HD in human iPSCs.

Navigating the epigenetic landscape of pluripotent stem cells.

Pluripotent stem cells, which include embryonic stem cells and induced pluripotent stem cells, use a complex network of genetic and epigenetic pathways to maintain a delicate balance between self-renewal and multilineage differentiation. Recently developed high-throughput genomic tools greatly facilitate the study of epigenetic regulation in pluripotent stem cells. Increasing evidence suggests the existence of extensive crosstalk among epigenetic pathways that modify DNA, histones and nucleosomes.

Cord blood-derived neuronal cells by ectopic expression of Sox2 and c-Myc.

The finding that certain somatic cells can be directly converted into cells of other lineages by the delivery of specific sets of transcription factors paves the way to novel therapeutic applications. Here we show that human cord blood (CB) CD133(+) cells lose their hematopoietic signature and are converted into CB-induced neuronal-like cells (CB-iNCs) by the ectopic expression of the transcription factor Sox2, a process that is further augmented by the combination of Sox2 and c-Myc. Gene-expression analysis, immunophenotyping, and electrophysiological analysis show that CB-iNCs acquire a distinct neuronal phenotype characterized by the expression of multiple neuronal markers.

Establishment of hepatic and neural differentiation platforms of Wilson's disease specific induced pluripotent stem cells.

The combination of disease-specific human induced pluripotent stem cells (iPSC) and directed cell differentiation offers an ideal platform for modeling and studying many inherited human diseases. Wilson's disease (WD) is a monogenic disorder of toxic copper accumulation caused by pathologic mutations of the ATP7B gene. WD affects multiple organs with primary manifestations in the liver and central nervous system (CNS).

Post-translational modulation of pluripotency.

The maintenance of pluripotency relies on an intricate transcriptional network hinged on a key set of transcription factors. Pluripotent stem cells have been shown to be sensitive to modulations of the cellular abundance and transcriptional activity of these key pluripotency factors. Recent evidence highlights the important role of post-translational modifications, including ubiquitination, sumoylation, phosphorylation, methylation, and acetylation, in regulating the levels and activity of pluripotency factors to achieve a balance between pluripotency and differentiation.

Higher-order genomic organization in pluripotent stem cells.

Recent applications of new tools for genome-wide mapping of long-range and spatial interactions have shed light onto the fundamental mechanisms of three dimensional chromatin organizations in pluripotent stem cells and their derivatives.